Roule V, Beygui F, Cayla G, Range G, Motovska Z, Delarche N, Jourda F, Goube P, Guedeney P, Zeitouni M, El Kasty M, Laredo M, Dumaine R, Ducrocq G, Derimay F, Van Belle E, Manigold T, Cador R, Combaret N, Vicaut E, Montalescot G, Silvain J; ALPHEUS investigators.
There is dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcome.
We aimed to assess the impact of the P2Y12 inhibitor loading time on peri-procedural myocardial necrosis in the population of the randomized ALPHEUS trial which compared ticagrelor to clopidogrel in high-risk elective PCI patients.
1809 patients of the ALPHEUS trial were divided into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 (a or b) myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 (a or b) myocardial infarction or any type of myocardial injury).
Patients in the first quartile group (Q1) presented higher rates of the primary outcome (p=0.01). When compared to Q1, incidences of the primary outcome decreased in patients with longer loading times (adjOR 0.70 [0.52.-0.95]; p=0.02 for Q2; adjOR 0.65 [0.48-0.88]; p<0.01 for Q3; adjOR 0.66 [0.49-0.89]; p<0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3%, and only one major bleeding at 48h) and clinical ischemic events were rare and did not differ between groups.
In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent peri-procedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.